Schizophrenia is a severe psychiatric illness that has a significant impact on patients,
their families, and society. It presents with deficits of different degrees in all
cognitive domains, including memory, processing speed, attention and executive functions,
which have been consistently demonstrated by different studies across several
geographical regions. This has implications for patients' social functioning and quality
of life, as cognitive symptoms together constitute the most important predictors of
patients' functioning in the community. Antipsychotic drugs, although effective for
psychotic symptoms, have little effect on cognition, however, cognitive rehabilitation
achieves at least a medium effect size to improve cognition. There are at least two
different cognitive remediation strategies, depending on the cognitive processes to which
the intervention is targeted. One has a "top-down" approach, and is aimed at higher-order
cognitive processes, and focuses on the training of executive functions. The other has a
"bottom-up" approach and aims to first recovering the perceptual processing alterations
that some patients with schizophrenia have and that would affect performance in
higher-order cognitive functions.
This study addresses in parallel two research questions, one of clinical interest, and
another focused on the psychological / neurobiological mechanisms of neurocognitive
remediation: What neurocognitive remediation strategy, executive skills training
("top-down" approach) or training perceptual approach ("bottom-up" approach), is it
effective in improving neurocognitive performance? Which neurocognitive remediation
strategies are related to changes in BDNF levels? At what point of the recovery process
are these changes observed? The hypothesis is that the "bottom-up" strategy presents
observable results at the end of the intervention, whereas the "top-down" strategy
results in an observable effect on neurocognitive performance and functioning in the
community in a delayed manner, 12 weeks after the intervention. We expect that both
strategies will be associated with an increase in BDNF levels compared to the situation
prior to the intervention, but that this will occur at the time when the clinical effect
is observed. The specific objectives are: (1) Evaluate the effectiveness of two cognitive
remediation strategies, one focused on executive skills training (top-down approach) and
another on perceptual training (bottom-up approach). (2) Study the critical moments of
neuroplasticity for each cognitive remediation strategy, observing changes in BDNF levels
at the end of the intervention and 12 weeks after the intervention. (3) Identify
potential clinical and/or molecular predictors (BDNF levels or val66met polymorphism) of
the response to treatment from the neurocognitive point of view for each cognitive
remediation strategy.
In order to achieve this, two randomized controlled trials with two arms will be carried
out in parallel, one where patients will receive cognitive remediation and another
consisting of a control group (with usual treatment). The control group subjects will
remain on a waiting and observation list for 10 weeks, to later enter the active arm,
which will also last 10 weeks. In one of the trials the active arm will consist of
cognitive remediation therapy with a "bottom-up" approach (focused on perceptual
training), while in the other trial the active arm will consist of cognitive remediation
with a "top-down" approach (focused on executive skills training). Neurocognitive and
clinical assessments will be carried out along with the measurement of BDNF levels at
four measurement times: one at baseline, one at the end of the observation period with
treatment-as-usual, another at the end of cognitive remediation, and another after a 12
weeks follow-up period.
